Our lab has identified an interesting relation between members of the Myc and E2f family of cell cycle regulators and chromatin changes and transcriptional regulation of differentiation of oligodendrocyte progenitors. We now propose to use primary cultures and genetic mouse models to test a new mechanistic model of oligodendrocyte differentiation. The results from the proposed experimental plan are likely to advance our knowledge not only in neural development and repair, but also in cancer and nuclear reprogramming and have wide implications for the development of novel therapeutic strategies.